单核细胞趋化蛋白-1和细胞间黏附分子-1与动脉粥样硬化和牙周病的关系

以动脉粥样硬化为病理基础的冠心病是目前主要的致死性疾病之一,而牙周病与动脉粥样硬化之间存在着一定的相关性。单核细胞趋化蛋白(MCP)-1和细胞间黏附分子(ICAM)-1在动脉粥样硬化和牙周病的发生发展中起着重要的作用。本文就MCP-1和ICAM-1以及二者与动脉粥样硬化、牙周病间的关系作一综述。     

Effects of Long-Term Pravastatin Treatment on Serum and Urinary Monocyte Chemoattractant Protein-1 Levels and Renal Function in Type 2 Diabetic Patients with Normoalbuminuria

To explore the renoprotective and anti-inflammatory effects of pravastatin, we analyzed the changes in renal function and urinary monocyte chemoattractant protein-1 (MCP-1) level as a renal tubulointerstitial inflammatory biomarker and serum MCP-1 level as a systemic inflammatory biomarker following the introduction of treatment with 10 mg/day of pravastatin in 10 hyperlipidemic type 2 diabetic patients with normoalbuminuria. Twelve months of the pravastatin treatment did not affect urinary levels of albumin, transferrin, N-acetylglucosaminidase, or MCP-1 in the hyperlipidemic diabetic patients, whereas the treatment significantly reduced serum levels of MCP-1 in the patients. The pravastatin treatment effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in the hyperlipidemic diabetic patients to levels nearly to those in 11 non-hyperlipidemic type 2 diabetic patients with normoalbuminuria. Interestingly, serum MCP-1 levels were significantly lower in the hyperlipidemic patients treated with pravastatin than in the non-hyperlipidemic patients. No significant correlation was observed between serum LDL-C and MCP-1 levels in all the data in the hyperlipidemic patients before and after the pravastatin treatment and in the non-hyperlipidemic patients. These results collectively indicate that pravastatin may ameliorate systemic vascular inflammation rather than local renal inflammation in hyperlipidemic type 2 diabetic patients with normoalbuminuria, independent of its cholesterol-lowering effects.     

MCP-1参与缬沙坦对阿霉素心脏毒性的预保护作用

目的　探讨阿霉素诱导SD大鼠心肌损伤模型中单核细胞趋化蛋白-1（MCP-1）蛋白表达及其潜在的干预机制。方法　选择8周龄雄性SPF级SD大鼠30只,按照随机数字表法分为3组：对照组（Con组,生理盐水灌胃＋腹腔注射）、阿霉素组（Dox组,1.25 mL/kg阿霉素腹腔注射+2 mL/kg生理盐水灌胃）及缬沙坦+阿霉素组（Val+Dox组,1.25 mL/kg阿霉素腹腔注射+2 mL/kg缬沙坦灌胃）各10只,连续干预6周。10周时超声心动图检测心功能变化,留取大鼠心肌组织,电镜观察心肌超微结构变化,采用蛋白芯片技术检测各组血清MCP-1、调节激活正常T细胞表达和分泌因子（RANTES）及次级淋巴组织趋化因子（6Ckine）蛋白含量,采用Western blot检测各组心肌组织MCP-1蛋白表达。结果　超声结果显示,与Con组相比,Dox组和Val+Dox组左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）明显降低,左心室收缩末期内径（LVESD）、左心室舒张末期内径（LVEDD）明显升高（P＜0.05）。与Dox组相比,Val+Dox组LVEF、LVFS明显升高,LVESD、LVEDD明显降低（P＜0.05）。电镜下可见Con组心肌细胞结构清晰;Dox组心肌结构模糊,心肌溶解,可见自噬小体;Val+Dox组心肌结构模糊不清,线粒体体积增大、大小不等,但结构完整。与Con组相比,Dox组血清MCP-1、RANTES、6Ckine蛋白分别上调1.87倍、1.40倍和1.26倍（P＜0.05）。Western blot结果显示,Dox组与Con组相比,心肌组织MCP-1蛋白表达显著升高（P＜0.05）;Val+Dox组与Dox组相比,心肌组织MCP-1蛋白表达显著降低（P＜0.05）。结论　MCP-1蛋白可能参与阿霉素诱导的心肌损伤,缬沙坦可能通过下调MCP-1蛋白表达减轻心肌损伤。     

外周血细胞计数及其比值预测百日咳患者疾病严重程度的分析

目的 ：评估外周血细胞计数[白细胞（white blood cell,WBC）、淋巴细胞绝对值、血小板（platelet,PLT）]及其相关比率,即中性粒细胞/淋巴细胞比率（neutrophil to lymphocyte ratio,NLR）、淋巴细胞与单核细胞比（lymphocyte to monocyte ratio,LMR）、血小板与淋巴细胞比率（platelet to lymphocyte ratio,PLR）、血小板计数与平均血小板体积（platelet count to mean platelet volume ratio,PLT/MPV）在预测百日咳患者合并呼吸道感染严重程度的价值。方法 ：回顾性分析1 129例百日咳患者资料,分组对比外周血WBC、PLT、NLR、PLR、LMR、PLT/MPV差异。结果：共1 129例患者纳入研究。重症肺炎组分别与3个非重症肺炎组（上呼吸道感染组、支气管炎组、肺炎组）WBC计数水平有统计学差异（P=0.000、0.041、0.000）,重症肺炎组WBC计数水平明显高于非重症肺炎的3组患者,WBC计数越高,越容易发生重症肺炎,提示外周血...     

Maternal obesity induced by a ‘cafeteria’ diet in the rat does not increase inflammation in maternal,placental or fetal tissues in late gestation

IntroductionObesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation.MethodsMaternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation.ResultsDespite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver.ConclusionsMaternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation.     

CD8+ T cells contribute to macrophage accumulation and airspace enlargement following repeated irritant exposure

BACKGROUND: Persistent macrophage accumulation and alveolar enlargement are hallmark features of chronic obstructive pulmonary disease (COPD). A role for CD8(+) lymphocytes in the development of COPD is suggested based on observations that this T cell subset is increased in the airways and parenchyma of smokers that develop COPD with airflow limitation. In this study, we utilize a mouse model of COPD to examine the contributions of CD8(+) T cells in the persistent macrophage accumulation and airspace enlargement resulting from chronic irritant exposure. METHODS: We analyzed pulmonary inflammation and alveolar destruction in wild-type and Cd8-deficient mice chronically exposed to acrolein, a potent respiratory tract irritant. We further examined cytokine mRNA expression levels by RNase protection assay, matrix metalloproteinase (MMP) activity by gelatin zymography, and epithelial cell apoptosis by active caspase3 immunohistochemistry in wild-type and Cd8-deficient mice exposed chronically to acrolein. RESULTS: These studies demonstrate that CD8(+) T cells are important mediators of macrophage accumulation in the lung and the progressive airspace enlargement in response to chronic acrolein exposures. The expression of several inflammatory cytokines (IP-10, IFN-gamma, IL-12, RANTES, and MCP-1), MMP2 and MMP9 gelatinase activity, and caspase3 immunoreactivity in pulmonary epithelial cells were attenuated in the Cd8-deficient mice compared to wild-type. CONCLUSIONS: These results indicate that CD8(+) T cells actively contribute to macrophage accumulation and the development of irritant-induced airspace enlargement.     

Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif

Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen that causes macrophage cell death by at least two different mechanisms. Rapid cell death is dependent on the Salmonella pathogenicity island-1 protein SipB whereas delayed cell death is independent of SipB and occurs 18-24 hr post infection. Lipopolysaccharide (LPS) is essential for the delayed cell death. LPS is the main structural component of the outer membrane of Gram-negative bacteria and is recognized by Toll-like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S. typhimurium induces SipB-independent cell death through Toll-like receptor 4 signalling via the adapter proteins Tram and Trif. In contrast to wild type bone marrow derived macrophages (BMDM), Tram(-/-) and Trif(-/-) BMDM proliferate in response to Salmonella infection.     

Trained immunity in organ transplantation

Consistent induction of donor‐specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen‐presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long‐term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro‐inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.     

房水中IL-6和MCP-1浓度与视网膜静脉阻塞合并黄斑水肿的相关性

目的：分析房水中白细胞介素-6(IL-6)和单核细胞趋化因子-1(MCP-1)浓度与视网膜静脉阻塞(RVO)合并黄斑水肿的相关性。

方法：选取2017-11/2019-11在内蒙古自治区人民医院确诊为RVO并接受玻璃体腔内注射雷珠单抗(IVR)治疗的患者40例40眼为治疗组,选取同期行白内障手术的单纯年龄相关性白内障患者20例20眼为对照组。采集两组患者房水,并检测房水中MCP-1和IL-6浓度。治疗组患者分别于首次IVR术前和术后1mo进行最佳矫正视力(BCVA)和黄斑区中心凹厚度(CMT)检测,分析术前房水中IL-6和MCP-1浓度及CMT的相关性。

结果：术前,治疗组患者房水中IL-6和MCP-1浓度(49.84±16.16、547.75±108.45pg/mL)明显高于对照组(10.71±7.26、235.65±34.45pg/mL,均P<0.001),且治疗组患者房水中IL-6和MCP-1浓度与CMT呈正相关(r=0.646、0.912,均P<0.001),IL-6与MCP-1浓度呈正相关(r=0.902,P<0.001)。首次IVR术后1mo,与术前相比,治疗组患者房水中IL-6、MCP-1浓度(20.08±11.56、228.35±70.69pg/mL)显著下降,BCVA和CMT明显改善(均P<0.001)。

结论：房水中IL-6和MCP-1浓度与RVO病变进程相关,玻璃体腔内注射雷珠单抗能够降低房水中IL-6和MCP-1的表达,降低CMT,减轻黄斑区水肿,改善视力。